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Managing Patients With Oncologic Complications in the ED

Managing Patients With Oncologic Complications in the ED

Whether a patient with cancer presents to the ED with cancer-treatment side effects or complications of the disease itself, timely diagnostic workup and evidence-based management strategies can make the difference in their quality of life. This issue reviews management recommendations for 3 ED presentations of oncologic patients: metastatic spinal cord compression, tumor lysis syndrome, and neutropenic fever. This issue will help you answer the following questions:

• What is the optimal imaging strategy for cancer patients with back pain? Should you go straight to MRI, or are plain radiographs a good first step?
• What is the difference between management of laboratory tumor lysis syndrome and clinical tumor lysis syndrome?
• Should the electrolyte derangements of tumor lysis syndrome be treated the same as for patients not in chemotherapy?
• What is the best method for collecting blood culture samples in cancer patients who present with fever?
• Do all patients with neutropenic fever need vancomycin?

Abstract

As the prevalence of cancer continues to increase in the general population and improvements in cancer treatment prolong survival, the incidence of patients presenting to the emergency department with oncologic complications will, similarly, continue to rise. This issue reviews 3 of the more common presentations of oncology patients to the emergency department: metastatic spinal cord compression, tumor lysis syndrome, and febrile neutropenia. Signs and symptoms of these conditions can be varied and nonspecific, and may be related to the malignancy itself or to an adverse effect of the cancer treatment. Timely evidence-based decisions in the emergency department regarding diagnostic testing, medications, and arrangement of disposition and oncology follow-up can significantly improve a cancer patient's quality of life.

Case Presentations

A 67-year-old man presents to the ED with a 5-day history of constant, dull, nonradiating, mid-lower back pain. He denies any alleviating factors or any specific movements or ambulation that worsen the pain. He denies numbness or weakness to his lower extremities, fevers, or bowel or bladder problems. His past medical history is significant for low-grade prostate cancer, diagnosed 2 years ago, which was managed by active surveillance only. On exam, his strength to both lower extremities seems diminished, his patellar reflexes are brisk, and his gait is unstable. He has no range-of-motion limitations to his back, but does complain of some midline tenderness at about the L1 level. Straight-leg raise is negative on both sides. His rectal tone is normal. At the conclusion of his exam, he states: “I really just came in to get something for the pain, doc. Can you prescribe me something so I can get going?” You wonder if he needs more testing...

A 55-year-old man with non–small-cell lung cancer presents after running a temperature of 38.5°C (101.3°F) at home. The fever lasted 3 hours and he denies other symptoms. He denies oral or rectal pain. He is currently undergoing chemotherapy for non–small-cell lung cancer; his last round was about 9 days ago. His additional past medical history is significant only for hypertension, though he is not on any medications for it. Family and social history are otherwise unremarkable. On exam, his vital signs are: temperature, 37.5°C (99.5°F); heart rate, 105 beats/min; respiratory rate, 25 breaths/min; blood pressure, 105/50 mm Hg; and oxygen saturation, 92% on room air. He is in no apparent distress, HEENT exam is normal except for mildly pale conjunctiva, lungs are clear, and heart and abdominal exam are unremarkable. External exam of the anus does not reveal evidence of perianal abscess. He has an indwelling peripherally inserted central catheter, and the site is well dressed, without stigmata of infection. Labs are remarkable for a white blood cell count of 0.6 cells/mm3 with neutrophil percentage of 10% and no bands. Hemoglobin is 7.1 g/dL, platelets are 45,000/mcL. Serum lactate is 2.9 mmol/L. Serum electrolytes, creatinine, liver function panel, and urinalysis are unremarkable. Chest x-ray shows a possible small infiltrate in the right base. The patient says he feels better overall, and asks if he needs to go home with any antibiotics, but you wonder if it is best practice to send him home...

Introduction

With increased life expectancy nationwide, the incidence and prevalence of cancer and cancer-related visits to the emergency department (ED) continue to rise. Evaluating patients for complications of malignancy or its treatment is obfuscated both by the often nonspecific presenting symptoms (eg, lethargy or encephalopathy) and the uncertainty about whether the symptoms are due to progression of the underlying disease or a complication of its therapy.1,2 This issue of Emergency Medicine Practice reviews the current state of diagnosis and ED treatment for metastatic spinal cord compression (MSCC), tumor lysis syndrome (TLS), and febrile neutropenia, focusing particularly on updates since the last time this topic was reviewed, in 2010.3,4

Critical Appraisal of the Literature

Because of the diversity of oncologic emergencies, we performed PubMed and MEDLINE® searches using terms specific to each emergency (eg, metastatic spinal cord compression, neutropenic fever, and tumor lysis syndrome), rather than simply searching for oncological emergencies. Particular attention was paid to articles published in the period since the original Emergency Medicine Practice articles on this subject in 2010. Our search yielded significant new literature on the topics of MSCC, TLS, and neutropenic fever, including updated guidelines for each of these, as well as several meta-analyses and large prospective randomized and observational studies. Despite our focus on topics with stronger evidence, in some instances, we had to rely more heavily on weaker evidence, such as case reports and expert opinion.

Risk Management Pitfalls for Oncologic Emergencies

2. “The spinal x-rays look normal. If she doesn’t have any metastasis, she couldn’t have cord compression.”

4. “Whoa, that patient with TLS has a calcium level of 8.0 mg/dL. He seems fine, but I’d better give him a little just to be sure.”

Avoid repletion of hypocalcemia in patients with TLS except in cases of cardiac arrhythmia or central nervous system involvement. Repletion of hypocalcemia in a setting of hyperphosphatemia will drive calcium phosphate crystal nephropathy.

9. “He has neutropenic fever, but he’s hemodynamically stable. I’d rather not start antibiotics until we know what it is we’re treating.”

In the treatment of patients with febrile neutropenia, empiric broad-spectrum antibiotic therapy should begin immediately, even if a specific diagnosis has not yet been made. For patients with high-risk features, a parenteral beta-lactam with antipseudomonal properties (such as cefepime or piperacillin-tazobactam) should be used. Additional antibiotics can be added specific to clinical suspicions (eg, metronidazole if C difficile is suspected).

Tables and Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of patients. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.

Jones GL, Will A, Jackson GH, et al. Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in Haematology. Br J Haematol. 2015;169(5):661-671. (Review article and clinical guideline)

Whether a patient with cancer presents to the ED with cancer-treatment side effects or complications of the disease itself, timely diagnostic workup and evidence-based management strategies can make the difference in their quality of life. This episode reviews management recommendations for 3 ED presentations of oncologic patients: metastatic spinal cord compression, tumor lysis syndrome, and neutropenic fever.

This episode of EB Medicine’s EMplify podcast is hosted by Jeff Nusbaum, MD, and Nachi Gupta, MD, PhD. This month’s corresponding full-length journal issue of Emergency Medicine Practice was authored by Dr. David Wacker and Dr. Michael McCurdy. It was peer reviewed by Dr. Karin Chase and Dr. Natalie Kreitzer.

Absolute Neutrophil Count (ANC) calculation is not a static measurement done only once upon hospital admission. Rather, it is often measured daily in critically ill patients (for example, to assess the bone marrow’s response after chemo­therapy).

Recall that the ANC is dynamic; it is an abso­lute value and is expected to drop during the patient’s nadir after chemotherapy.

The ANC can be calculated with a routine complete blood cell (CBC) count and differential. No additional laboratory work is needed to complete the calculation. It is a tool that provides rapid risk stratification.

When To Use

The ANC can be critical in assessing an immunocompromised patient’s risk for developing opportunistic infections. It is commonly used in the hospital setting, clinic, and emergency department.

If a patient undergoing active myelosuppressive chemotherapy presents with a sustained fever (with or without localizing symptoms), there is a risk of progression to sepsis. Thus, it is imperative to calculate the ANC to help decide whether empiric antibiotics should be initiated.

Next Steps

Neutropenic fever (without a source of infection found) is typically the result of direct toxic effects of chemotherapy on mucosal surfaces and the immune system, in addition to the impact of the underlying malignancy. It is defined as a single oral temperature of ≥ 38.3ºC (100.9ºF), or a sustained temperature of > 38ºC (100.4ºF) for over 1 hour in a patient with neutropenia. Neutropenic fever is typically seen in those who have received anticancer therapies in the last 6 weeks. Filgrastim (Neupogen®, Zarxio®), also known as G-CSF, can stimulate production of neutrophils, but is rarely indicated in the evaluation and treatment of neutropenic fever.

Additional tools to risk stratify a neutropenic fever patient and predict complications include the Clinical Index of Stable Febrile Neutropenia (CISNE) score and the Multinational Association for Supportive Care in Cancer (MASCC) score.

Obtain a complete blood count with differential.

ANC is calculated as 10 x WBC count in 1000s x (% PMNs + % bands)

Classify neutropenia as mild, moderate, or severe according to the following:Neutropenia: ANC < 1500 cells/mm.

Mild neutropenia: 1000-1500 cells/mm³

Moderate neutropenia: 500-999 cells/mm³

Severe neutropenia: < 500 cells/mm³.

ANC values also can be interpreted by NCI risk categories, as in the table below:

If the clinical scenario is suggestive of neutropenic fever, appropriate cultures and infectious disease workup should be instituted along with prompt initiation of empiric broad-spectrum antibiotics to cover mostly endogenous flora.

Al-Gwaiz et al (2007) tested the application of ANC to predict bacterial infections. They examined 105 peripheral blood smears and determined ANC, as well as the sensitivity of predicting bacterial infec­tions. They determined that the ANC and toxic granulations are more sensitive than band count in predicting bacterial infections. Rivera et al (2003) performed a cross-validation study of Silber et al's 1998 findings to test if the first-cycle nadir ANC pre­dicted the risk of febrile neutropenia. An ANC of ≤ 0.5 x 109/L was associated with a relative odds ratio of 4.8. The goal of this study was to provide a foundation for which dose adjustments in chemo­therapy can be made to provide maximal anti-neo­plastic therapy while minimizing side effects.

Use in neutropenic patients with a fever of at least 38ºC (100.4°F). Do not use in patients with acute leukemia who are undergoing induction chemother­apy or allogeneic hematopoietic stem cell transplant conditioning, per IDSA guidelines.

The Multinational Association for Supportive Care in Cancer (MASCC) risk index applies only to adult patients.

It is validated as a dichotomous outcome: low-risk versus not-low-risk. Obviously, patients who are “not-low-risk” have varying degrees of risk.

Why and When to Use, and Next Steps

Why To Use

Febrile neutropenia is a potentially life-threatening complication of chemotherapy, but some patients are at low risk for serious complications. The MASCC risk index is an internationally validated scoring system that identifies these low-risk patients who can potentially be treated as outpatients with early antibiotics.

When To Use

Use at onset of fever, to assess the risk of complications in febrile neutropenia for patients undergoing chemotherapy treatment.

Use after addressing immediate concerns, to identify patients who may not need to be admitted to the hospital or could be discharged early.

Next Steps

Higher scores indicate lower risk, with a maximum of 26 points. Using a cutoff value of ≥ 21 points dis­criminates patients with low risk from those with high risk (< 21 points) for serious complications of febrile neutropenia, eg, death, admission to the intensive care unit, or hypotension.

The MASCC score has been endorsed by the IDSA since 2002 with Level B (moderate) evidence support­ing its use. However, most experts consider high-risk patients to be those with anticipated prolonged neutropenia (> 7 days), profound neutropenia (absolute neutrophil count < 100), and/or comorbid condi­tions (in addition to chronic obstructive pulmonary disease) – Level A evidence – that are not necessarily accounted for in the MASCC score. Therefore, clinical judgment by specialists (in infectious disease, he­matology/oncology, or emergency medicine/internal medicine/critical care) with knowledge of predicted disease-specific chemotherapy effects may override the MASCC score.

High-risk patients require admission for intravenous antibiotics.

Carefully selected low-risk patients should receive oral or intravenous empiric antibiotics in a clinic or hospital setting, and may be transitioned to outpatient regimens if they meet certain criteria.

The derivation study for the MASCC risk index was performed in the late 1990s (1994-1997) and included 756 patients in the derivation cohort and 383 patients in the validation cohort. While many claim that the MASCC risk index cannot be applied to patients with hematologic malignancies, over 40% of the patients included in the study had a he­matologic malignancy. Logistic regression analysis was used to determine a weighted risk score with a positive predictive value (PPV) of 91%, specificity of 68%, and sensitivity of 71%.

Of note, patients were only included in the study for a single episode of febrile neutropenia and were not allowed to re-enter the study for subsequent episodes; thus, it is unclear whether the score should be applied to patients with multiple episodes of febrile neutropenia, although this is routinely done in clinical practice.

There have been at least 8 external validation studies showing a PPV from 83% to 98% with sensi­tivity from 59% to 95%. Studies that included more patients with hematologic malignancies had lower PPV and sensitivity, suggesting a poorer perfor­mance of the score in that population.

Use in neutropenic patients with a fever of at least 38ºC (100.4°F). Do not use in patients with acute leukemia who are undergoing induction chemother­apy or allogeneic hematopoietic stem cell transplant conditioning, per IDSA guidelines.

Publication Date

CME Expiration Date

CME Information

Identify conditions due to cancer or cancer therapy that have the potential to cause death or organ damage.

Initiate treatment for oncologic emergencies, including providing immediate therapies in the emergency department and establishing plans for definitive management.

Make disposition decisions appropriate to patient condition and expected prognosis.

Physician CME Information

Date of Original Release: January 1, 2018. Date of most recent review: December 10, 2017. Termination date: January 1, 2021.

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ACEP Accreditation: Emergency Medicine Practice is approved by the American College of Emergency Physicians for 48 hours of ACEP Category I credit per annual subscription.

AAFP Accreditation: This Enduring Material activity, Emergency Medicine Practice, has been reviewed and is acceptable for credit by the American Academy of Family Physicians. Term of approval begins 07/01/2017. Term of approval is for one year from this date. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Approved for 4 AAFP Prescribed credits.

AOA Accreditation: Emergency Medicine Practice is eligible for up to 48 American Osteopathic Association Category 2-A or 2-B credit hours per year.

Specialty CME: Included as part of the 4 credits, this CME activity is eligible for 1 Pharmacology CME credit, subject to your state and institutional approval.

Needs Assessment: The need for this educational activity was determined by a survey of medical staff, including the editorial board of this publication; review of morbidity and mortality data from the CDC, AHA, NCHS, and ACEP; and evaluation of prior activities for emergency physicians.

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